Ethyl Acetate → Methyl 2-(4-hydroxyphenyl)-2-[(thiophen-3-yl)methylamino]acetate

HRID 1919787Notes

Reaction equation

HRID 1919787 reaction equation
Cl.[NH2:2][C@H:3]([C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1)[C:4]([O:6][CH3:7])=[O:5].C(OCC)(=O)C.S([O-])([O-])(=O)=O.[Mg+2].[S:27]1[CH:31]=[CH:30][C:29]([CH:32]=O)=[CH:28]1>C(N(CC)CC)C>[OH:14][C:11]1[CH:10]=[CH:9][C:8]([CH:3]([NH:2][CH2:32][C:29]2[CH:30]=[CH:31][S:27][CH:28]=2)[C:4]([O:6][CH3:7])=[O:5])=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 24083Sulfuric acid magnesium salt (1:1)HCID 681353-ThiophenecarboxaldehydeHCID 13215089Methyl (2R)-amino(4-hydroxyphenyl)acetate--hydrogen chloride (1/1)

Product 1

HCID 59235192Methyl 2-(4-hydroxyphenyl)-2-[(thiophen-3-yl)methylamino]acetate

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

5 g of methyl(R)-amino-(4-hydroxyphenyl)acetate hydrochloride and 100 mL of anhydrous ethyl acetate (thick suspension) are introduced at ambient temperature into a 500 mL Woulff bottle equipped with a nitrogen intake, a magnetic stirrer and a condenser. 3.1 mL of triethylamine, some magnesium sulphate and 3 g of thiophene-3-carbaldehyde are added. After 4 hours under reflux, the white solid is filtered, washed with ethyl acetate and dried under vacuum. The product is taken up in 100 mL of anhydrous dichloromethane. 14 g of sodium triacetoxy borohydride are added and the mixture is stirred at ambient temperature for 2 hours. 100 mL of methanol are added then the reaction mixture is concentrated. The product is extracted with ethyl acetate. It is washed with water then the organic phases are dried over magnesium sulphate. The mixture is concentrated, and the residue is purified over a silica column with 50/50 heptane/ethyl acetate. After concentration and crystallisation in isopropanol, a white solid is obtained (2.35 g; Yd=37%).

Workup

  1. customequipped with a nitrogen intake, a magnetic stirrer and a condenser
  2. temperatureAfter 4 hours under reflux
  3. filtrationthe white solid is filtered
  4. washwashed with ethyl acetate
  5. customdried under vacuum
  6. addition14 g of sodium triacetoxy borohydride are added
  7. addition100 mL of methanol are added
  8. concentrationthe reaction mixture is concentrated
  9. extractionThe product is extracted with ethyl acetate
  10. washIt is washed with water
  11. dry with materialthe organic phases are dried over magnesium sulphate
  12. concentrationThe mixture is concentrated
  13. customthe residue is purified over a silica column with 50/50 heptane/ethyl acetate
  14. concentrationAfter concentration and crystallisation in isopropanol
  15. customa white solid is obtained (2.35 g; Yd=37%)

Sources & evidence

ORD record
ord-03c19b4740844ffdb1c01a3364730101
Source dataset
uspto-grants-2012_05
Patent number
US08168667B2

Reaction notes

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